Thursday, October 20, 2011

On October 17, a judge in the Southern District of California issued a significant claim construction ruling in the case of Biogen Idec and Genentech v. GlaxoSmithKline. The plaintiffs allege that defendants anti-CD20 monoclonal antibody Ofatumumab (trade name Arzerra) infringes US patent number 7,682,612. Plaintiffs market a competing anti-CD20 antibody, Rituximab (trade name Rituxan).

Based on my understanding of the case, the ruling appears to be a substantial victory for GlaxoSmithKline.

The disputed claim terms are found in claim 1 of the patent, which recites:

1. A method of treating chronic lymphocytic leukemia in a human patient, comprising administering an anti-CD20 antibody to the patient in an amount effective to treat the chronic lymphocytic leukemia, wherein the method does not include treatment with a radiolabeled anti-CD20 antibody.

The court construed the terms "anti-CD20 antibody” and “CD20 binding fragment” as “rituximab and antibodies that bind to the same epitope of the CD20 antigen with similar affinity and specificity as rituximab” and "the portion of the anti-CD20 antibody that binds to the same epitope of the CD20 antigen with similar affinity and specificity as rituximab.” This is significant, because Arzerra does not bind to the same epitope as rituximab, which appears to rule out infringement if this construction of the terms is affirmed on appeal.

The plaintiffs argued for a broader construction, such that the disputed terms would cover any antibody that binds to CD20, even antibodies that bind to different epitopes, such as Arzerra. However, the court found that the prosecution history of the patent established that during prosecution plaintiffs represented that the claims were limited to antibodies binding to the same epitope as rituximab, and the court held them to this more limited construction of the term.

The court also construed the terms "does not include treatment with a radiolabeled anti-CD20 antibody" and "radiation is not used" as "excludes the use of a radiolabeled anti-CD20 antibody or the administration of a separate radiolabeled anti-CD20 antibody," and "no form of radiation (including radiolabeled antibodies) is used," respectively. This construction is significant, because it appears to rule out infringement when Arzerra is used in conjunction with Bexxar or Zevalin, which are both radiolabeled anti-CD20 antibodies.

Wednesday, October 19, 2011

Yesterday Pioneer Hi-Bred (a subsidiary of DuPont) sued Monsanto, its rival in the agricultural biotechnology sector, for allegedly infringing its patents directed towards a method of increasing "seed vigor" in maize that entails defoliating maize plants during a specific period after pollination. The lawsuit was filed in the Southern District of Iowa, Pioneer's home territory.

The two companies have been involved in a high-profile patent litigation ever since Pioneer announced its plans to release genetically modified maize comprising Pioneers Optimum GAT trait stacked with Monsanto's Roundup Ready trait. Both traits confer resistance to glyphosate (i.e. Roundup), albeit by different mechanisms - Roundup Ready essentially works by rendering the plant resistant to glyphosate, while Optimum GAT causes the plant to express a protein that breaks down the glyphosate molecule.

Pioneer responded by suing Monsanto for antitrust violations, based on the company’s licensing and enforcement practices with respect to its patents covering the Roundup Ready trait. The patent infringement case is scheduled to go to trial next June, while the antitrust counterclaims are scheduled to go to trial April 2013.

The two patents being asserted by Pioneer in the most recent lawsuit are US patent numbers 5,518,989 and 6,162,974. The ‘989 patent claims a method of increasing seed vigor in maize by defoliating plants during a specific time window after pollination, based upon how long the growing plant has been exposed to warm days. The ‘974 patent claims an "assemblage" of maize seeds produced using the method. Here are a couple of representative claims.

Claim 1 from the ‘989 patent:

1. A method for treating a stand of maize plants, comprising the steps of

(A) reducing functional leaf area in substantially all of said plants, wherein said reducing is effected at between about 600 and about 850 GDDs after pollination of said plants, and then

(B) harvesting said stand, such that a seed assemblage is obtained from said stand that is characterized by a level of seed vigor that is enhanced relative to the level of seed vigor in a seed assemblage harvested from a comparison stand of maize plants not subjected to said reducing of functional leaf area.

Claim 1 from the ‘974 patent:

1. A maize seed assemblage having enhanced seed vigor, wherein said seed assemblage is obtained by the method comprising the steps of:

(a) reducing functional leaf area in substantially all of a stand of maize plants, wherein said reducing is effected at between about 600 and about 850 GDDs after pollination of said plants, and

(b) harvesting said stand to obtain an assemblage of seeds,

wherein said seed assemblage is characterized by a level of seed vigor that is enhanced relative to the level of seed vigor in a seed assemblage harvested from a comparison stand of maize plants not subjected to said reducing of functional leaf area.

According to Wikipedia, “GDD [,which stands for Growing Degree Day, is] a measure of heat accumulation used by horticulturists, gardeners, and farmers to predict plant and pest development rates such as the date that a flower will bloom or a crop reach maturity.” Wikipedia states that "plants grow in a cumulative stepwise manner which is strongly influenced by the ambient temperature. Growing degree days take aspects of local weather into account and allow gardeners to predict (or, in greenhouses, even to control) the plants’ pace toward maturity."

The patents state that "functional leaf area can be reduced" (i.e., the plant can be defoliated) using mechanical or chemical means. "Chemical means" would include treatment with an herbicide such as Roundup (the dependent claims explicitly identify Roundup as an herbicide to be used in the method.

The patents remind me of the patents at issue in In re Cruciferous Sprouts litigation that occurred several years ago. In that case, as I recall, researchers at Johns Hopkins University discovered that cruciferous sprouts (e.g., broccoli sprouts) harvested at a particular point in time after germination (in particular, prior to the "two-leaf stage") contain high levels of certain compounds believed to be useful in preventing cancer.

A representative claim at issue in that case recited " “A method of preparing a food product rich in glucosinolates, comprising germinated cruciferous seeds, with the exception of cabbage, cress, mustard and radish seeds, and harvesting sprouts prior to the 2-leaf stage, to form a food product comprising a plurality of sprouts.”

The Federal Circuit held that the claims were invalid based on inherent anticipation. Although the Johns Hopkins researchers might have been the first to recognize the health benefits of eating cruciferous sprouts harvested prior to the two-leaf stage, in fact people had been eating sprouts harvested at this stage for many years. This was surely the correct result - if the claims were held valid, that would mean that Johns Hopkins would have the right to exclude others from doing something that had long been part of the prior art, i.e., eating broccoli sprouts and the like.

The same sort of issue of inherent anticipation could potentially be raised with respect to Pioneer's patents on methods of defoliating maize plants at a certain time after pollination. It would seem to me that if Monsanto can show that, prior to Pioneers invention, maize plants had been defoliated during this stage of growth (perhaps by treatment with Roundup), a court might come to the conclusion that the claims are inherently anticipated.

The claims also might raise issues of patent eligibility, at least in the minds of people like Justice Breyer. Recall that in his LabCorp dissent Justice Breyer expressed a view that a patent claim that preempts substantially all practical use of a newly discovered natural phenomenon is patent ineligible. Some might characterize Pioneer’s discovery that defoliation of maize at a certain time results in increased seed vigor as the discovery of a "natural phenomenon," and conclude that Pioneer’s claims effectively preempt all substantial practical application of this discovery.

Pioneer's claims directed towards a "maize seed assemblage" might also raise patent eligibility issues. The claimed maize seeds are arguably not genetically modified, in which case they might be considered "products of nature" and not patent eligible under Chakrabarty. In order to be patent eligible, it would seem that a court would have to determine that either the defoliation resulted in a "man-made" seed, or that grouping seeds in an "assemblage" is sufficient human intervention to establish patent eligibility.

Wednesday, October 5, 2011

Meganucleases are endodeoxyribonucleases characterized by a large recognition site (double-stranded DNA sequences of 12 to 40 base pairs); as a result this site generally occurs only once in any given genome. For example, the 18-base pair sequence recognized by the I-SceI meganuclease would on average require a genome twenty times the size of the human genome to be found once by chance. Meganucleases are therefore considered to be the most specific naturally occurring restriction enzymes.

The high specificity of meganucleases gives them a high degree of precision and much lower cell toxicity than other naturally occurring restriction enzymes; they were identified in the 1990s as particularly promising tools for genome engineering.

However, the meganuclease-induced genetic recombinations that could be performed were limited by the repertoire of meganucleases available. Despite the existence of hundreds of meganucleases in nature, and the fact that each one is able to tolerate minor variations in its recognition site, the probability of finding a meganuclease able to cut a given gene at the desired location is extremely slim. Several research laboratories therefore soon began trying to engineer new meganucleases targeting the desired recognition sites.

Cellectis and Precision Biosciences are two competing biotechnology companies, both seeking to commercialize engineered meganucleases for use in genetic engineering.

On March 1, 2011, Cellectis sued Precision Biosciences in the District Court of Delaware for allegedly infringing US patent number 7,897,372, directed to "I-CreI Meganuclease Variants with Modified Specificity.” That case is presently proceeding with discovery, and trial is set for February 2013.

On September 20, 2011, the US patent office issued US patent number 8,021,867, which is directed towards "Rationally-Designed Meganucleases with Altered Sequence Specificity and DNA-Binding Affinity." The named assignee on the patent is Duke University, but according to Celectis the patent is actually owned by Precision.

On September 30, 2011, Cellectis filed another lawsuit against Precision Biosciences, again in the District Court of Delaware, and this time it is a declaratory judgment action seeking a declaration that the Duke/Precision patent is invalid and not infringed by Cellectis.

In the complaint, Cellectis does not allege that it has explicitly been threatened with a lawsuit by Precision. Instead, it argues that declaratory judgment is appropriate because: both patents-in-suit concern the same field of technology, i.e., "modified" or "altered" I-CreI meganucleases; the Cellectis patent is prior art to the precision patent, the parties in both cases are the same, and the discovery in both cases likely would substantially overlap.

About Me

I am a law professor at the University of Missouri-Kansas City School of Law. My primary research interests lie at the intersection of biotechnology and intellectual property. This blog provides analysis and commentary on recent developments relevant to this area of the law.